I wanted to share an educational discussion on cell studies being performed at an annual meeting of medical professionals
The article is geared to kids 15 to 19
What I find interesting are the questions being asked at the end of the discussion
Upon first reading I felt that it was educational but the questions at the end of the article shed light on the true importance of this meeting of the minds and their potential goals to understanding cancers and other mechanics of the human body
The folks writing the discussion as follows
Daniel Irimia is an Assistant Professor at Massachusetts General Hospital and Harvard Medical School, USA, studying how the ability of cells to migrate contributes to health and disease. His interests range from the role of white blood cell migration in protecting tissues against microbes to the role of cancer cell migration during cancer invasion and metastasis. For these studies, he is designing robust micro-scale tools to measure cell migration with high precision from clinically relevant samples. The World Cell Race organising team also includes Matthieu Piel from the Institut Curie and CNRS in France, and Elisabeth Wong and Bashar Hamza, both from Massachusetts General Hospital.
The questions and the potential of this study
Suitable comprehension questions could include:
1) What is the importance of the study of cell motility?
2) What is the relationship between cell motility and cell migration?
3) What is the aim of the World Cell Race?
4) Why does the shape of the race track change from one year to another in the World Cell Race?
5) Give some examples of cells in which it would benefit researchers to stop motility or to encourage motility.
6) Some cells make self-guided movements and don’t seem to need any stimuli to move. What kinds of cells are they? Why are they considered to pose a problem?
7) Using the race track, how would you prove the effect of a drug on cell motility?
http://www.scienceinschool.org/print/4268
"Making the right moves ". Discussion on cell movement
Re: "Making the right moves ". Discussion on cell movement
Hi all again
Wanted to expand on this discussion and maybe bring it closer to home. Alveolar soft part sarcoma
Within the discussion it states-
"Other cells, like the ones included in the cell race, move in a much less dramatic way by creating membrane protrusions (called pseudopodia), a bit like reaching fingers, which attach themselves to a surface and then pull the rest of the cell along behind them (see figure 1). A cell moving this way can typically cover 1-2 times its own length per hour. To put this into context, a snail moves at around 20 body lengths per hour; in his record-breaking sprint at the 2012 Olympic Games, Usain Bolt ran at the equivalent of 18 000 body lengths per hour."
NIH link to studies on pseudopodia protrusins and mestatic cancers
" Pseudopodial Actin Dynamics Control Epithelial-Mesenchymal Transition in Metastatic Cancer Cells"
http://cancerres.aacrjournals.org/conte ... /3780.long
Discussion from link-
Based on the fundamental requirement of pseudopod protrusion for tumor cell migration and metastasis, we used a combined transcriptomics and proteomics approach to identify 19 pseudopod-specific proteins in six metastatic cell lines of varying tumor origin, including breast, prostate, fibrosarcoma, and glioma. Knockdown of four pseudopod-enriched proteins, AHNAK, septin-9, eIF4E, and S100A11, resulted in pseudopod retraction, inhibition of cell migration and invasion, reduced actin cytoskeleton dynamics, and reversion of EMT. Our data define a direct link between pseudopodial actin dynamics and EMT, and suggest that targeting molecules crucial for pseudopod formation, such as those identified in this study, might represent a means to revert EMT, inducing mesenchymal-epithelial transition (MET), and potentially inhibiting tumor cell metastasis.
Ingenuity pathway analysis of the cohorts of pseudopodial mRNAs and proteins in individual cell lines as well as those common to all six metastatic cell lines showed a high degree of cancer relevance (Fig. 1C). Expression of many of the 19 pseudopod-enriched proteins has been linked to various cancers. eIF4E has a well-established role in the progression of multiple cancer types and is actively being assessed as a therapeutic target for cancer therapy (26, 28). Expression of septin 9 is associated with malignant brain tumors (29). Higher levels of S100A11 expression are associated with colorectal cancer progression and invasion and metastasis of non–small cell lung cancer (30, 31). AHNAK was originally identified in neuroblastoma cancer cell lines; however, detailed study of its role in human cancers remains limited (32). Several other pseudopod-enriched proteins have also been reported to be associated with cancer including COTL1, YWHAE, ATP synthase, TPM4, SET, PTMA, and CNN2 (33–38). Importantly, many of the identified proteins (Table 1), such as COTL1, YWHAE, TPM4, CNN2, septin 9, AHNAK, S100A11, and eIF4E, have well-defined associations with the actin cytoskeleton (39–45). In addition, we also identified five ribosomal proteins (RPL11, RPL23, RPL6A, RPL13, and RPL27) that, together with pseudopodial enrichment of eIF4E, elongation factor α (46), and various other proteins associated with RNA translocation and protein translation (19), further supports actin-rich pseudopodia as sites of active protein translation. This domain-specific transcriptome and proteome analysis across multiple metastatic cancer cells of various tissue origins has therefore resulted in the identification of actin-associated proteins of potential cancer relevance.
Knockdown of each of these proteins reduces cellular F-actin content, actin turnover rate, and pseudopodial protrusion (Fig. 6), consistent with the established role of a dynamic actin cytoskeleton in pseudopod protrusion, as well as tumor cell migration and invasion. This suggests that they all act to promote pseudopod protrusion through a common mechanism associated with actin turnover and actin cytoskeleton remodeling. Although the specific relevance of each of the identified pseudopod-enriched proteins in cancer progression remains to be determined, this study underlies the critical importance of pseudopodial actin dynamics in the migratory and invasive phenotypes critical to tumor metastasis.
The fact that depletion of these proteins results in the reversion of EMT is of particular interest and links pseudopodial actin dynamics to transitions between epithelial and mesenchymal cell phenotypes. Indeed, the ability of actin stabilization with jasplakinolide to restore the expression of EMT markers after pseudopod protein knockdown suggests that a stable actin cytoskeleton is critical for EMT in cancer cells. Pseudopod protrusion is observed upon ErbB2-driven EMT in epithelial cells and may underlie increased invasiveness observed during EMT (47). E-cadherin binding to p120-catenin plays a fundamental role in the stability of epithelial cell-cell adhesions and regulates actin assembly required for the formation of membrane protrusions (48). However, although membrane protrusion formation is associated with EMT-driven cell invasion, there is to date no experimental evidence directly linking EMT to pseudopod formation (49). How pseudopodial actin dynamics are regulating EMT is unclear. However, the ability of a relatively short (2 hours) actin stabilization with jasplakinode to revert MET suggests that it is related not to transcriptional activity and gene regulation but rather to the regulation of local protein turnover that might be involved in the EMT process. That regulation of actin dynamics by both pseudopodial proteins and pharmacologic agents controls the expression of EMT markers defines for the first time, to our knowledge, the critical role of actin dynamics and pseudopodial protrusion and, therefore, the acquisition of a motile, migratory phenotype, on the induction of EMT.
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Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Wanted to expand on this discussion and maybe bring it closer to home. Alveolar soft part sarcoma
Within the discussion it states-
"Other cells, like the ones included in the cell race, move in a much less dramatic way by creating membrane protrusions (called pseudopodia), a bit like reaching fingers, which attach themselves to a surface and then pull the rest of the cell along behind them (see figure 1). A cell moving this way can typically cover 1-2 times its own length per hour. To put this into context, a snail moves at around 20 body lengths per hour; in his record-breaking sprint at the 2012 Olympic Games, Usain Bolt ran at the equivalent of 18 000 body lengths per hour."
NIH link to studies on pseudopodia protrusins and mestatic cancers
" Pseudopodial Actin Dynamics Control Epithelial-Mesenchymal Transition in Metastatic Cancer Cells"
http://cancerres.aacrjournals.org/conte ... /3780.long
Discussion from link-
Based on the fundamental requirement of pseudopod protrusion for tumor cell migration and metastasis, we used a combined transcriptomics and proteomics approach to identify 19 pseudopod-specific proteins in six metastatic cell lines of varying tumor origin, including breast, prostate, fibrosarcoma, and glioma. Knockdown of four pseudopod-enriched proteins, AHNAK, septin-9, eIF4E, and S100A11, resulted in pseudopod retraction, inhibition of cell migration and invasion, reduced actin cytoskeleton dynamics, and reversion of EMT. Our data define a direct link between pseudopodial actin dynamics and EMT, and suggest that targeting molecules crucial for pseudopod formation, such as those identified in this study, might represent a means to revert EMT, inducing mesenchymal-epithelial transition (MET), and potentially inhibiting tumor cell metastasis.
Ingenuity pathway analysis of the cohorts of pseudopodial mRNAs and proteins in individual cell lines as well as those common to all six metastatic cell lines showed a high degree of cancer relevance (Fig. 1C). Expression of many of the 19 pseudopod-enriched proteins has been linked to various cancers. eIF4E has a well-established role in the progression of multiple cancer types and is actively being assessed as a therapeutic target for cancer therapy (26, 28). Expression of septin 9 is associated with malignant brain tumors (29). Higher levels of S100A11 expression are associated with colorectal cancer progression and invasion and metastasis of non–small cell lung cancer (30, 31). AHNAK was originally identified in neuroblastoma cancer cell lines; however, detailed study of its role in human cancers remains limited (32). Several other pseudopod-enriched proteins have also been reported to be associated with cancer including COTL1, YWHAE, ATP synthase, TPM4, SET, PTMA, and CNN2 (33–38). Importantly, many of the identified proteins (Table 1), such as COTL1, YWHAE, TPM4, CNN2, septin 9, AHNAK, S100A11, and eIF4E, have well-defined associations with the actin cytoskeleton (39–45). In addition, we also identified five ribosomal proteins (RPL11, RPL23, RPL6A, RPL13, and RPL27) that, together with pseudopodial enrichment of eIF4E, elongation factor α (46), and various other proteins associated with RNA translocation and protein translation (19), further supports actin-rich pseudopodia as sites of active protein translation. This domain-specific transcriptome and proteome analysis across multiple metastatic cancer cells of various tissue origins has therefore resulted in the identification of actin-associated proteins of potential cancer relevance.
Knockdown of each of these proteins reduces cellular F-actin content, actin turnover rate, and pseudopodial protrusion (Fig. 6), consistent with the established role of a dynamic actin cytoskeleton in pseudopod protrusion, as well as tumor cell migration and invasion. This suggests that they all act to promote pseudopod protrusion through a common mechanism associated with actin turnover and actin cytoskeleton remodeling. Although the specific relevance of each of the identified pseudopod-enriched proteins in cancer progression remains to be determined, this study underlies the critical importance of pseudopodial actin dynamics in the migratory and invasive phenotypes critical to tumor metastasis.
The fact that depletion of these proteins results in the reversion of EMT is of particular interest and links pseudopodial actin dynamics to transitions between epithelial and mesenchymal cell phenotypes. Indeed, the ability of actin stabilization with jasplakinolide to restore the expression of EMT markers after pseudopod protein knockdown suggests that a stable actin cytoskeleton is critical for EMT in cancer cells. Pseudopod protrusion is observed upon ErbB2-driven EMT in epithelial cells and may underlie increased invasiveness observed during EMT (47). E-cadherin binding to p120-catenin plays a fundamental role in the stability of epithelial cell-cell adhesions and regulates actin assembly required for the formation of membrane protrusions (48). However, although membrane protrusion formation is associated with EMT-driven cell invasion, there is to date no experimental evidence directly linking EMT to pseudopod formation (49). How pseudopodial actin dynamics are regulating EMT is unclear. However, the ability of a relatively short (2 hours) actin stabilization with jasplakinode to revert MET suggests that it is related not to transcriptional activity and gene regulation but rather to the regulation of local protein turnover that might be involved in the EMT process. That regulation of actin dynamics by both pseudopodial proteins and pharmacologic agents controls the expression of EMT markers defines for the first time, to our knowledge, the critical role of actin dynamics and pseudopodial protrusion and, therefore, the acquisition of a motile, migratory phenotype, on the induction of EMT.
Previous Section
Next Section
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Debbie